Heterogeneous Distribution of Proton Motive Force in Nonheritable Antibiotic Resistance

Lee, Annie H.; Gupta, Rachit; Nguyen, Hong Nhi; Schmitz, Isabella R; Siegele, Deborah A.; Lele, Pushkar P.

doi:10.1128/mbio.02384-22

Cited by 5 publications

(16 citation statements)

References 69 publications

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“…The cells were then suspended in lethal concentrations of ampicillin for three hours (see Materials and Methods ). A significant fraction of the cells tolerated the ampicillin exposure and several cells retained motility, consistent with earlier studies ( 32, 34, 53 ). We again washed the tolerant cells to remove ampicillin and loaded them into the microfluidic chamber while simultaneously observing the channels.…”

Section: Resultssupporting

confidence: 90%

“…Our recent study suggests that rifampicin induces a bifurcation of the tolerant population: nearly one out of three tolerant cells continued to swim rapidly in lethal concentrations of ampicillin for several hours, while the rest were nonmotile ( 32 ). As motility requires the PMF, which also produces ATP during aerobic respiration, this suggested that a significant fraction of the tolerant cells might not be dormant.…”

Section: Resultsmentioning

confidence: 99%

“…First, we treated the smooth-swimming strain with a lethal concentration of rifampicin for 30 min. We washed the cells in the growth media to remove the rifampicin, following earlier protocols ( 32, 53 ). The cells were then suspended in lethal concentrations of ampicillin for three hours (see Materials and Methods ).…”

Section: Resultsmentioning

confidence: 99%

“…Remarkably, our recent results demonstrate that almost 30-40% of tolerant E. coli cells generated by the rifampicin treatment retain motility in the presence of ampicillin and other antibiotics for several hours ( 32 ). This suggests that not all tolerant cells lack cellular energy, consistent with previous studies ( 35–38 ).…”

Section: Introductionmentioning

confidence: 96%

“…Another powerful adaptation mechanism intrinsic to many bacterial species involves efflux pumps that expel the antibiotic ( Fig 1 ). These pumps utilize the proton-motive force (PMF), which also powers cellular growth and several functions, such as motility and ATP synthesis ( 32, 33 ).…”

Section: Introductionmentioning

confidence: 99%

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Dynamic Adaptation in Extant Porins Facilitates Antibiotic Tolerance in EnergeticEscherichia coli

Mukhopadhyay,

Bishayi,

Shaji

et al. 2024

Preprint

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Bacteria can tolerate antibiotics despite lacking the genetic components for resistance. The prevailing notion is that tolerance results from depleted cellular energy or cell dormancy. In contrast to this view, many cells in the tolerant population of Escherichia coli can exhibit motility- a phenomenon that requires cellular energy, specifically, the proton-motive force (PMF). As these motile-tolerant cells are challenging to isolate from the heterogeneous tolerant population, their survival mechanism is unknown. Here, we discovered that motile bacteria segregate themselves from the tolerant population under micro-confinement, owing to their unique ability to penetrate micron-sized channels. Single-cell measurements on the motile-tolerant population showed that the cells retained a high PMF, but they did not survive through active efflux alone. By utilizing growth assays, single-cell fluorescence studies, and chemotaxis assays, we showed that the cells survived by dynamically inhibiting the function of existing porins in the outer membrane. A drug transport model for porin-mediated intake and efflux pump-mediated expulsion suggested that energetic tolerant cells withstand antibiotics by constricting their porins. The novel porin adaptation we have uncovered is independent of gene expression changes and may involve electrostatic modifications within individual porins to prevent extracellular ligand entry.

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Section: Resultssupporting

confidence: 90%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Dynamic Adaptation in Extant Porins Facilitates Antibiotic Tolerance in EnergeticEscherichia coli

Mukhopadhyay,

Bishayi,

Shaji

et al. 2024

Preprint

Self Cite

View full text Add to dashboard Cite

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Inactivation of Listeria monocytogenes, Escherichia coli O157:H7, and Staphylococcus aureus by sequential light-emitting diodes (LEDs) treatment at 365 nm and 420 nm

Xiao,

Zhang

2025

Food Research International

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Decoding Bacterial Persistence: Mechanisms and Strategies for Effective Eradication

Sett,

Dubey,

Bhowmik

et al. 2024

ACS Infect. Dis.

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The ability of pathogenic bacteria to evade antibiotic treatment is an intricate and multifaceted phenomenon. Over the years, treatment failure among patients due to determinants of antimicrobial resistance (AMR) has been the focal point for the research and development of new therapeutic agents. However, the survival of bacteria by persisting under antibiotic stress has largely been overlooked. Bacterial persisters are a subpopulation of sensitive bacterial cells exhibiting a noninheritable drug-tolerant phenotype. They are linked to the recalcitrance of infections in healthcare settings, in turn giving rise to AMR variants. The importance of bacterial persistence in recurring infections has been firmly recognized. Fundamental work over the past decade has highlighted numerous unique tolerance factors contributing to the persister phenotype in many clinically relevant pathogens. This review summarizes contributing factors that could aid in developing new strategies against bacterial antibiotic persisters.

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Heterogeneous Distribution of Proton Motive Force in Nonheritable Antibiotic Resistance

Abstract: Bacterial cells with low PMF may survive antibiotic stress due to dormancy, which favors nonheritable resistance without genetic mutations or acquisitions. On the other hand, cells with high PMF are less tolerant, as PMF helps in the uptake of certain antibiotics.

Cited by 5 publications

References 69 publications

Dynamic Adaptation in Extant Porins Facilitates Antibiotic Tolerance in EnergeticEscherichia coli

Dynamic Adaptation in Extant Porins Facilitates Antibiotic Tolerance in EnergeticEscherichia coli

Inactivation of Listeria monocytogenes, Escherichia coli O157:H7, and Staphylococcus aureus by sequential light-emitting diodes (LEDs) treatment at 365 nm and 420 nm

Decoding Bacterial Persistence: Mechanisms and Strategies for Effective Eradication

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